RU2006106205A - AMINOCHINOLINE DERIVATIVES AND THEIR APPLICATION AS Adenosine A3 Ligands - Google Patents

Claims (21)

1. Compounds of General Formula (I)

in which R ¹ represents a hydrogen atom or a linear or branched C _1-4 alkyl group; R ² represents a hydrogen atom or a linear or branched C _1-4 alkyl group; R ³ represents a hydrogen atom or a linear or branched C _1-4 alkyl group, a C _3-6 cycloalkyl group, a phenyl, thienyl or furyl group optionally substituted with one or more linear or branched C _1-4 alkyl group, a linear or branched C _1-4 alkoxygroup or halogen atom; a six- or five-membered heteroaromatic ring containing one, two or three nitrogen atoms, or a five-membered heteroaromatic ring containing one nitrogen atom and one oxygen atom, or one nitrogen atom and one sulfur atom, optionally substituted with one or more linear or a branched C _1-4 alkyl group, a linear or branched C _1-4 alkoxy group or a halogen atom; R ⁴ and R ⁵ independently represent a hydrogen atom, a C _3-6 cycloalkyl group, a linear or branched C _1-4 alkyl group, optionally containing an amino group or an amino group substituted by one or two linear or branched C _1-4 alkyl groups a hydroxy group, a carboxy group or an alkoxy group substituted with a linear or branched C _1-4 alkyl group; or R ⁴ represents a hydrogen atom or a linear or branched C _1-4 alkyl group or benzyl group; and R ⁵ represents a hydrogen atom, a —SO ₂ OH group or a linear or branched C _1-4 acyl group; or R ⁴ and R ⁵ together with a nitrogen atom form a group of the general formula (a)

in which R ⁷ and R ⁸ independently from each other represent a hydrogen atom, a linear or branched C _1-4 alkyl group or a C _3-6 cycloalkyl group; R ⁶ represents a hydrogen atom or a linear or branched C _1-4 alkyl group, a phenyl, benzyl, thienyl or furyl group, optionally substituted with a methylenedioxy group or one or more linear or branched C _1-4 alkyl group, a linear or branched C _1-4 alkoxy group, hydroxy group, triflumethyl group, cyano group or a halogen atom; or a six- or five-membered heteroaromatic ring containing one, two or three nitrogen atoms, or one nitrogen atom and one oxygen atom, or one nitrogen atom and one sulfur atom, optionally substituted with one or more linear or branched C _1-4 alkyl a group, a linear or branched C _1-4 alkoxy group or a halogen atom; X represents a —CH ₂ group, —NH group, —NR ⁹ group or a sulfur atom, an oxygen atom, a sulfo group or a sulfoxy group, where R ⁹ represents a linear or branched C _1-4 alkyl group or a C _3-6 cycloalkyl group; Z represents an oxygen atom, a sulfur atom, a group —CHR ¹⁰ or a group —NR ¹¹ in which R ¹⁰ represents a hydrogen atom, a linear or branched C _1-4 alkyl group or a C _3-6 cycloalkyl group, and R ¹¹ represents a hydrogen atom, a linear or branched C _1-4 alkyl group, a C _3-6 cycloalkyl group, a —SO ₂ OH group or a linear or branched C _1-4 acyl group; n is zero, 1 or 2; m is 1, 2 or 3; o is 1, 2 or 3; p is zero or 1; r is zero or 1, and their salts, solvates, isomers (tautomers, desmotropic forms, optically active isomers), as well as their salts and solvates. 2. The compounds of General formula (I) according to claim 1, in which R ¹ represents a hydrogen atom or a linear or branched C _1-4 alkyl group; R ² represents a hydrogen atom or a linear or branched C _1-4 alkyl group; R ³ represents a hydrogen atom or a linear or branched C _1-4 alkyl group, a C _3-6 cycloalkyl group, a phenyl, thienyl or furyl group optionally substituted with one or more linear or branched C _1-4 alkyl group, a linear or branched C _1-4 alkoxygroup or halogen atom; R ⁴ and R ⁵ independently represent a hydrogen atom, a C _3-6 cycloalkyl group, a linear or branched C _1-4 alkyl group, optionally containing an amino group or an amino group substituted by one or two linear or branched C _1-4 alkyl groups a hydroxy group, a carboxy group or an alkoxy group substituted with a linear or branched C _1-4 alkyl group; or R ⁴ represents a hydrogen atom or a linear or branched C _1-4 alkyl group or benzyl group; and R ⁵ represents a hydrogen atom, a —SO ₂ OH group or a linear or branched C _1-4 acyl group; or R ⁴ and R ⁵ together with a nitrogen atom form a group of the general formula (a) in which R ⁷ and R ⁸ independently represent a hydrogen atom, a linear or branched C _1-4 alkyl group or a C _3-6 cycloalkyl group; R ⁶ represents a hydrogen atom or a linear or branched C _1-4 alkyl group, a phenyl, benzyl, thienyl or furyl group, optionally substituted with a methylenedioxy group or one or more linear or branched C _1-4 alkyl group, a linear or branched C _1-4 alkoxy group, hydroxy group, triflumethyl group, cyano group or a halogen atom; or a six- or five-membered heteroaromatic ring containing one, two or three nitrogen atoms, or one nitrogen atom and one oxygen atom, or one nitrogen atom and one sulfur atom, optionally substituted with one or more linear or branched C _1-4 alkyl a group, a linear or branched C _1-4 alkoxy group or a halogen atom; X represents a —CH ₂ group, —NH group, —NR ⁹ group or a sulfur atom, an oxygen atom, a sulfo group or a sulfoxy group, where R ⁹ represents a linear or branched C _1-4 alkyl group or a C _3-6 cycloalkyl group; Z represents an oxygen atom, a sulfur atom, a group —CHR ¹⁰ or a group —NR ¹¹ in which R ¹⁰ represents a hydrogen atom, a linear or branched C _1-4 alkyl group or a C _3-6 cycloalkyl group, and R ¹¹ represents a hydrogen atom, a linear or branched C _1-4 alkyl group, a C _3-6 cycloalkyl group, an —SO ₂ OH group or a formyl group; n is zero, 1 or 2; m is 1, 2 or 3; o is 1, 2 or 3; p is zero or 1; r is zero or 1, and their salts, solvates, isomers (tautomers, desmotropic forms, optically active isomers), as well as their salts and solvates. 3. The compounds of General formula (I) according to claim 2, in which R ¹ represents a hydrogen atom or a methyl group; R represents a hydrogen atom or a methyl group; R ³ represents a phenyl, thienyl or furyl group; R ⁴ and R ⁵ independently represent a hydrogen atom, a C _3-6 cycloalkyl group, a linear or branched C _1-4 alkyl group, optionally containing an amino group or an amino group substituted by one or two linear or branched C _1-4 alkyl groups a hydroxy group, a carboxy group or an alkoxy group substituted with a linear or branched C _1-4 alkyl group; or R ⁴ represents a hydrogen atom or a linear or branched C _1-4 alkyl group or benzyl group; and R ⁵ represents a hydrogen atom, a —SO ₂ OH group or a formyl group; or R ⁴ and R ⁵ together with a nitrogen atom form a group of general formula a, in which R ⁷ and R ⁸ independently represent a hydrogen atom, a linear or branched C _1-4 alkyl group or a C _3-6 cycloalkyl group; R ⁶ represents a 4-methoxyphenyl, 3-methylphenyl, 3-methoxyphenyl, 3,4-methylenedioxyphenyl, 4-fluorophenyl, 2-thienyl or 2-furyl group; X represents an —NH group or an oxygen atom; Z represents an oxygen atom, a sulfur atom, a —CH ₂ group, an —NH group or an —NR ¹¹ group in which R ¹¹ represents a linear or branched C _1-4 alkyl group, a C _3-6 cycloalkyl group, an —SO ₂ group OH or formyl group; and n is 1; m is 2; o is 2; p is zero; r is zero and their salts, solvates, isomers (tautomers, desmotropic forms, optically active isomers), as well as their salts and solvates. 4. The compounds according to claim 3, which are 4-methoxy-N- [6- (morpholin-4-yl) -4-benzylamino-3-cyanoquinolin-2-yl] benzamide; 4-methoxy-N- [6- (4-methylpiperazin-1-yl) -4-benzylamino-3-cyanoquinolin-2-yl] benzamide; 4-methoxy-N- (6-dimethylamino-4-benzylamino-3-cyanoquinolin-2-yl) benzamide; 3,4-methylenedioxy-N- (6-dimethylamino-4-benzylamino-3-cyanoquinolin-2-yl) benzamide; 4-fluoro-N- (6-dimethylamino-4-benzylamino-3-cyanoquinolin-2-yl) benzamide; 4-methoxy-N- (6- (piperazin-1-yl) -4-benzylamino-3-cyanoquinolin-2-yl) benzamide; 4-methoxy-N- (6-amino-4-benzylamino-3-cyanoquinolin-2-yl) benzamide; N- [4- (benzylamino) -3-cyano-6- (4-formylpiperazin-1-yl) quinolin-2-yl] -4-methoxybenzamide; 4- {4- (benzylamino) -3-cyano-2 - [(4-methoxybenzoyl) amino] quinolin-6-yl} piperazine-1-sulfonic acid; N- {3-cyano-6- (formylamino) -4 - [(2-thienylmethyl) amino] quinolin-2-yl} -4-methoxybenzamide; N- {3-cyano-6- (formylamino) -4 - [(2-thienylmethyl) amino] quinolin-2-yl} -1,3-benzodioxol-5-carboxamide; N- [4- (benzylamino) -3-cyano-6- (formylamino) quinolin-2-yl] -1,3-benzodioxol-5-carboxamide; N- [4- (benzylamino) -3-cyano-6- (formylamino) quinolin-2-yl] -4-methoxybenzamide; N- {4- (benzylamino) -3-cyano-6- [formyl (methyl) amino] quinolin-2-yl} -4-methoxybenzamide; N- {3-cyano-6- [formyl (methyl) amino] -4 - [(2-thienylmethyl) amino] quinolin-2-yl} -4-methoxybenzamide; {3-cyano-2 - [(4-methoxybenzoyl) amino] -4 - [(2-thienylmethyl) amino] quinolin-6-yl} methylsulfamic acid; {4- (benzylamino) -3-cyano-2 - [(4-methoxybenzoyl) amino] quinolin-6-yl} methylsulfamic acid; {4- (benzylamino) -3-cyano-2 - [(4-methoxybenzoyl) amino] quinolin-6-yl} sulfamic acid; [2 - [(1,3-benzodioxol-5-ylcarbonyl) amino] -4- (benzylamino) -3-cyanoquinolin-6-yl] sulfamic acid; {2 - [(1,3-benzodioxol-5-ylcarbonyl) amino] -3-cyano-4 - [(2-thienylmethyl) amino] quinolin-6-yl} sulfamic acid; {3-cyano-2 - [(4-methoxybenzoyl) amino] -4 - [(2-thienylmethyl) amino] quinolin-6-yl} sulfamic acid, and their salts, solvates, isomers (tautomers, desmotropic forms), as well as their salts and solvates. 5. A method of obtaining compounds of General formula (I)

and their salts, solvates and isomers, where R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , X, Z, n, o, p, r and m have the meanings defined in claim 1, characterized in that v) bis-carboxamide of General formula (II ")

in which R ^{1 "} represents a hydrogen atom or a linear or branched C _1-4 alkyl group; R ^{2 "} represents a hydrogen atom or a linear or branched C _1-4 alkyl group; R ^{3 "} represents a hydrogen atom or a linear or branched C _1-4 alkyl group, a C _3-6 cycloalkyl group, a phenyl, thienyl or furyl group optionally substituted with one or more linear or branched C _1-4 alkyl group, linear or branched C _1-4 alkoxy group or a halogen atom; a six- or five-membered heteroaromatic ring containing one, two or three nitrogen atoms, or five-membered heteroaromatic ring containing one nitrogen atom and one oxygen atom or one nitrogen atom and one atom of Ser Optionally substituted with one or more linear or branched C _1-4 alkyl group, a linear or branched C _1-4 alkoxy group or a halogen atom; R ^{4 "} and R ^5" independently represent a hydrogen atom, a C _3-6 cycloalkyl group, a linear or branched C _1-4 alkyl group, optionally containing an amino group or an amino group substituted by one or two linear or branched C _1-4 alkyl groups, a hydroxy group, a carboxy group or an alkoxy group substituted with a linear or branched C _1-4 alkyl group, or a protecting group; or R ^{4 "} represents a hydrogen atom or a linear or branched C _1-4 alkyl group or benzyl group; and R ^{5 "} represents a hydrogen atom, a —SO ₂ OH group or a linear or branched C _1-4 acyl group or a protecting group; or R ^{4 "} and R ^5" together with the nitrogen atom form a nitro group or a group of the general formula (a) in which R ^{7 "} and R ^8" independently represent a hydrogen atom, a linear or branched C _1-4 alkyl group or C _3-6 cycloalkyl group; R ^{6 "} represents a hydrogen atom or a linear or branched C _1-4 alkyl group, a phenyl, benzyl, thienyl or furyl group optionally substituted with a methylenedioxy group or one or more linear or branched C _1-4 alkyl group, a linear or branched C _{1- 4} alkoxy, hydroxy, triftometilnoy group, cyano group or halogen atom, or six- or five-membered heteroaromatic ring containing one, two or three nitrogen atoms, or one nitrogen atom and one oxygen atom, or one atom az the one and one sulfur atom, optionally substituted by one or more linear or branched C _1-4 alkyl group, a linear or branched C _1-4 alkoxy group or a halogen atom; X "represents a group —CH ₂ , a group —NH, a group —NR ⁹ or a sulfur atom, an oxygen atom, a sulfo group or a sulfoxy group, where R ^9" represents a linear or branched C _1-4 alkyl group or a C _3-6 cycloalkyl group ; Z "represents an oxygen atom, a sulfur atom, a group -CHR ^10" or a group -NR ^{11 "} , in which R ^10" represents a hydrogen atom, a linear or branched C _1-4 alkyl group or a C _3-6 cycloalkyl group, and R ^{11 ″} represents a hydrogen atom, a linear or branched C _1-4 alkyl group, a C _3-6 cycloalkyl group, a —SO ₂ OH group or a linear or branched C _1-4 acyl group; n "is zero, 1 or 2; m "is 1, 2 or 3; o "is 1, 2 or 3; p "is zero or 1; r "is zero or 1, selectively hydrolyze and, if desired, remove the protective group, or v / i) for the preparation of compounds of general formula (I) in which R ⁴ represents a hydrogen atom or a linear or branched C _1-4 alkyl group or a benzyl group, and R ⁵ represents a linear or branched C _1-4 acyl group, or R ⁴ and R ⁵ together with a nitrogen atom form a group of the general formula (a) in which Z represents a —NR ¹¹ group, where R ¹¹ represents a linear or branched C _1-4 acyl group, and R ¹ , R ² , r ^3, r ^6, r ^7, r ^8, r ^9, X, n, m, o, p and r are as defined above, a compound of general formula (I), wherein r ⁴ is a hydrogen atom, a linear or branched C _1-4 alkyl group or benzyl group and R ⁵ represents a hydrogen atom, or R ⁴ and R ⁵ together with the nitrogen atom form a group of the general formula (a) wherein Z represents a group -NH and R ¹ , R ² , R ³ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , X, n, m, o, p, and r are as defined above, acylated with a compound of the general formula R ^{12 "} COY" in which R ^{12 "} and Y" have the meanings defined above, or v / ii) to obtain a compound of general formula (I) in which R ⁴ represents a hydrogen atom, a linear or branched C _1-4 alkyl group or a benzyl group, and R ⁵ represents a —SO ₂ OH or R ⁴ group and R ⁵ together with a nitrogen atom form a group of the general formula (a) in which Z represents a —NR ¹¹ group, where R ¹¹ represents a —SO ₂ OH group, and R ¹ , R ² , R ³ , R ⁶ , R ⁷ , r ^8, r ^9, X, n, m, o, p and r are as defined above, a compound of general formula (I), wherein r ⁴ represents a hydrogen atom, a linear or branched C _1-4 alkyl group yl benzyl group and R ⁵ represents a hydrogen atom, or R ⁴ and R ⁵ together with the nitrogen atom form a group of the general formula (a) wherein Z represents a -NH group and R ^1, R ^2, R ^3, R ^6, R ⁷ , R ⁸ , R ⁹ , X, n, m, o, p and r are as defined above, are reacted with a pyridine-SO ₃ complex or with ClSO ₃ H, or v / iii) to obtain a compound of general formula (I) in which R ⁴ represents a hydrogen atom, a linear or branched C _1-4 alkyl group or a benzyl group, and R ⁵ represents a —SO ₂ OH group, and R ¹ , R ² , R ³ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , X, Z, n, m, o, p and r are as defined above, the compound of general formula (XIII ")

in which R ¹ , R ² , R ³ , R ⁶ , R ⁹ , X and n are as defined above, reacted with Na ₂ S ₂ O ₄ or NaHSO ₃ , or the resulting compound of general formula (XIV ")

in which R ^{4 "} represents a hydrogen atom, and R ^1" , R ^{2 "} , R ^3" , R ^{6 "} , R ^9" , X ^" and n" are as defined above, sulfonated with a pyridine-SO ₃ or ClSO complex ₃ H, and, if desired, then convert the hydrogen atom R ^{4 "} into a linear or branched C _1-4 alkyl group or benzyl group; or v / iv) for the preparation of compounds of general formula (I) in which R ⁴ represents a hydrogen atom, a C _3-6 cycloalkyl group, a benzyl group, a linear or branched C _1-4 alkyl group, optionally containing an amino group or an amino group substituted with one or two linear or branched C _1-4 alkyl groups, an alkoxy group, a carboxy group or an alkoxy group substituted with a linear or branched C _1-4 alkyl group, and R ⁵ represents a hydrogen atom, or R ⁴ and R ⁵ together with a nitrogen atom form a group formulas (a) in to Torah R ⁷ and R ⁸ each independently represent a hydrogen atom, a linear or branched C _1-4 alkyl group or C _3-6 cycloalkyl group and Z represents a group -NR ^11, wherein R ¹¹ represents a hydrogen atom, remove the protective group of the compounds of General formula (I '), in which R ^{4 "} represents a C _1-4 cycloalkyl group, a benzyl group, a linear or branched C _1-4 alkyl group, optionally containing an amino group or an amino group substituted by one or two linear or branched C _1-4 alkyl groups, a hydroxy group, a carboxy group or an alkoxy group substituted with a linear or branched C _1-4 alkyl group, and R ⁵ is a protecting group; or R ^{4 "} and R ^5" together with a nitrogen atom form a group of the general formula (a "), in which R ^{7 "} and R ^8" independently from each other represent a hydrogen atom, a linear or branched C _1-4 alkyl group or a C _3-6 cycloalkyl group, and Z represents a group -NR ^{11 "} , in which R ^11" represents a protective group, and, if desired, the substituents in the obtained compound of the general formula (I) are converted into each other by known methods and / or the compounds of the general formula (I) thus obtained are converted into their salts or solvates, or released from the salts or solvates, and, if desired, split into their optically active isomers, and, if desired, this desmotropic form is converted to another desmotropic form. 6. The method according to claim 5, characterized in that the selective hydrolysis is carried out with an alkali metal hydroxide dissolved in an alcohol medium, preferably a methanolic solution of potassium or sodium hydroxide. 7. A pharmaceutical composition, characterized in that it contains one or more compounds of the general formula (I), in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , X, Z , n, m, o, p and r have the meanings defined in claim 1, and / or their salts, solvates, isomers (tautomers, desmotropic forms, optically active isomers), their salts, solvates and one or more auxiliary substances, commonly used in the pharmaceutical industry. 8. The pharmaceutical composition according to claim 7, characterized in that it contains as an active substance one or more of the compounds defined in claim 3. 9. The use of compounds of General formula (I), their salts, solvates and isomers, where R ¹ , R ² , R ³ , R ^" , R ⁵ , R ⁶ , R ⁷ , R ⁸ , X, Z, n, m, o, p and r have the meanings defined in claim 1, for the manufacture of a pharmaceutical composition for the treatment of diseases in the development of which the A ₃ receptor plays a role. 10. The use of compounds of General formula (I), their salts, solvates and isomers according to claim 9, where R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , X, Z, n, m, o, p and r have the meanings defined in claim 1, as A ₃ ligands for the manufacture of a pharmaceutical composition for the treatment of heart, kidney, respiratory and central nervous system diseases and for inhibiting the protection of adenosine in growing tumor cells, prevention of mast cell degranulation, inhibition of cytokine production, reduction of intraocular pressure, inhibition of TNFα release, inhibiting Ia migration of eosinophils, neutrophils and other immune cells, inhibition of bronchoconstriction and plasma extravasation. 11. The use of compounds of General formula (I), their salts, solvates and isomers of claim 10, where R ¹ , R ² , R ³ , R ₄ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , X, Z, n, m, o, p and r have the meanings defined in claim 1, as antagonists of A ₃ receptors for the manufacture of anti-inflammatory, anti-asthma, anti-ischemic drugs, antidepressants, antiarrhythmic drugs, kidney protectants, anti-tumor drugs, anti-parkinsonism drugs and cognitive enhancing pharmaceutical compositions and compositions for treating or preventing reperfusion myocardial damage, chronic obstructive pulmonary disease (COPD), and adult respiratory distress syndrome (ARDS), including chronic bronchitis, pulmonary emphysema or shortness of breath, allergic reactions (e.g., rhinitis, toxic ivy-induced reactions, urticaria, scleroderma, arthritis), other autoimmune diseases, inflammatory bowel diseases, Addison’s disease, Crohn’s disease, psoriasis, rheumatism, hypertension, functional neurological disorders, glaucoma and diabetes. 12. The use of compounds of general formula (I), their salts, solvates and isomers according to claims 10 and 11, where R ¹ , R ² , R ³ , R ₄ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , X, Z, n, m, o, p and r have the meanings defined in claim 1 as antagonists of A ₃ receptors for the manufacture of pharmaceutical compositions for the treatment of diseases such as asthma, COPD and ARDS, glaucoma, tumors, allergic reactions, inflammatory diseases, ischemia, hypoxia, arrhythmia and renal disease. 13. Compounds of General formula (I ")

in which R ^{1 "} , R ^2" , R ^{3 "} , R ^6" , R ^{7 "} , R ^8" , X ^" , n", m ", o", p "and r" have the meanings defined in paragraph 5, and R ^{4 "} represents a hydrogen atom, a C _3-6 cycloalkyl group, a benzyl group, a linear or branched C _1-4 alkyl group, optionally containing an amino group or an amino group substituted by one or two linear or branched C _1-4 alkyl groups, a hydroxy group, a carboxy group or an alkoxy group substituted with a linear or branched C _1-4 alkyl group; and R ^{5 "} represents a protecting group; or R ^{4 "} and R ^5" together with a nitrogen atom form a group of the general formula (a "), in which R ^7" and R ^{8 "} independently represent a hydrogen atom, a linear or branched C _1-4 alkyl group or C _{3 A -6} cycloalkyl group; and Z represents a group —NR ^{11 ″} , where R ^{11 ″} represents a protecting group. 14. Compounds of General Formula (II ")

in which R ^{1 "} , R ^2" , R ^{3 "} , R ^4" , R ^{5 "} , R ^6" , R ^{7 "} , R ^8" , X ", Z", n ", m", o ", p "and r" have the meanings defined in clause 5. 15. Compounds of General Formula (III ")

in which R ^{1 "} , R ^2" , R ^{3 "} , R ^4" , R ^{5 "} , R ^7" , R ^{8 "} , X", Z ", n", m ", o", p "and r" have the meanings defined in clause 5. 16. Compounds of General Formula (IV ")

in which R ^{4 "} , R ^5" , R ^{7 "} , R ^8" , Z ^" , m", o ", p" and r "have the meanings defined in clause 5. 17. Compounds of General Formula (V ")

in which R ^{4 "} , R ^5" , R ^{7 "} , R ^8" , Z ", m", o ", p" and r "have the meanings defined in clause 5. 18. Compounds of General Formula (VI ")

in which R ^{4 "} , R ^5" , R ^{7 "} , R ^8" , Z ", m", o ", p" and r "have the meanings defined in paragraph 5, provided that R ^4" and R ^{5 "} together with the nitrogen atom have values different from the dimethylamino and amino groups. 19. Compounds of General Formula (VII ")

in which R ^{4 "} , R ^5" , R ^{7 "} , R ^8" , Z ", m", o ", p" and r "have the meanings defined in paragraph 5, provided that R ^4" and R ^{5 "} together with the nitrogen atom have values different from the dimethylamino, diethylamino and amino groups. 20. Compounds of General Formula (VIII ")

in which R ^{4 "} and R ^5" together with the nitrogen atom represent a morpholino, N-methylpiperazino, piperazino or 4-benzylpiperazino group. 21. Compounds of General Formula (XIII ")

in which the substituents R ^{1 "} , R ^2" , R ^{3 "} , R ^6" and n "have the meanings defined in paragraph 5.